ABSTRACT Confocal microscopy has allowed a large number of biomedical researchers in the Departments of Neuroscience and Psychiatry & Behavioral Sciences at the Medical University of South Carolina (MUSC) to elucidate morphological and protein neuroadaptations in rodent models of neuropsychiatric diseases. A number of these investigators are recognized leaders in the field of addiction neurosciences, and a major focus of the faculty in these departments is to understand human disease using innovative approaches. The faculty identified in this application are currently using a 15-year-old and technologically obsolete confocal microscope. There are recent advances in confocal imaging technology that provide substantial improvements in speed, sensitivity, and resolution over the current capabilities of the existing confocal microscope. Thus, the overall goal of this application is to upgrade the obsolete confocal and create a Shared Confocal Facility equipped with a new versatile and high-resolution confocal microscope system that will serve the faculty in the Departments of Neuroscience, Psychiatry & Behavioral Sciences, and other departments at MUSC. We propose to replace the older system with a Zeiss LSM 880 that has an Airyscan detector capable of superresolution imaging. Unlike our current system, the versatile Zeiss LSM 880 has an open interface and modular architecture that will allow reconfiguration of the system as our future needs change to meet the rigorous demands of biomedical research. Moreover, our preliminary data show that images acquired with a superresolution detector are far superior in quality and resolution, and quantitation of superresolution images revealed an increase in the density of fine dendritic protrusions (i.e., dendritic spines) compared with the same images acquired with a GaAsP detector. These qualitative and quantitative findings strongly demonstrate the necessity of this state-of-the-art technology to allow the investigators to examine cellular structures and relationships of proteins with enhanced detail. There is substantial institutional support provided by the Departments of Neuroscience and Psychiatry & Behavioral Sciences and Office of the Provost at MUSC to cover the instrument for its lifetime and to expand image analysis capabilities in an effort to facilitate superresolution technology on MUSC's campus. In addition to supporting individual R01 awards, two NIH-funded P50 Center grants, and two NIH-funded T32 Training grants at MUSC, the superresolution confocal will provide data to two national consortia (Integrative Neuroscience Initiative on Alcoholism and Neurobiology of Adolescent Drinking in Adulthood). Thus, this upgrade will immediately influence the current research programs at MUSC and across the US, and will provide users with equipment that can grow and change in parallel with cutting-edge neuroscience research. A technological upgrade of this magnitude will be critical in furthering the long-range biomedical research goals at the Medical University of South Carolina.